Diabetes mellitus affects approximately 4.5 million Americans, causing serious disability and premature death in most patients with diabetes of more than 10 years' duration. Microvascular angiopathy, the cause of the relentless complications of longstanding diabetes, cannot be effectively prevented nor controlled with the use of exogenous insulin. Typical manifestations of diabetic microangiopathy are seen in the eye (microaneurysms, hemorrhages, cataracts, and, ultimately, blindness) and in the kidney (mesangial proliferation, basement membrane thickening, immunoglobulin deposition, nodular glomerulosclerosis, and renal dysfunction). We propose to study the feasibility of physiologic control of diabetes in the subhuman primate through transplantation of the endocrine pancreas (isolated islets of Langerhans). Specific areas of investigation will include: 1. Demonstrations of typical microangiopathy with ocular and renal lesions, in the rhesus monkey made diabetic with streptozotocin, as an appropriate model for study of human disease. Other metabolic parameters such as glucagon levels, somatostatin effect, serum lipid abnormalities, platelet aggregation studies, and cardiovascular dysfunction (hypertension, myocardial disease) will be documented. Endogenous and exogenous insulin levels will be measured with a C-peptide insulin assay. 2. Isolation of viable and functional beta cell preparations from the primate pancreas (adult and fetal). 3. Autotransplantation of isolated viable islet preparations in order to establish the practicality of physiologic functional reconstitution of the totally pancreatectomized host. 4. Allotransplantation of islet preparations into diabetic monkeys, using techniques of histocompatibility testing for donor-recipient matching, and immunosuppression with drugs and heterologous antithymocyte serum. The long-term effects of development of microangiopathy will be assessed.